The primary objective of the proposed studies is to elucidate the processes of hepatic bile acid transport and bile secretion. The primary approach to this problem is (1) to vary bile acid chemical structure, (2) to test the physico-chemical effects of these variations, (3) to test the physiological response of the cat or rat liver to these variations. In the cat we will measure bile acid phospholipid, cholesterol and water secretion rates in response to bile acid infusion. In the rat we will measure hepatic transport rates. The correlation of physico-chemical properties and physiologic responses should help us to understand the intracellular processes. Two subsidiary aims will be (1) to test the hypothesis that CAMP synthesis is an intermediate step in the formation of the bile and (2) to purify and characterize an hepatic cytoplasmic protein which binds bile acids. The former study involves the measurement of CAMP, by radioimmunoassay, in plasma, during acid induced choleresis. The latter requires the gel chromatographic purification of a cytoplasmic protein in rat liver and the subsequent determination of its bile acid binding characteristics - the number and affinity of bile acid binding sites. The structure of the protein and its physiologic role would then be determined.